Triacyl-phenylpropaneaminodiols



James, 1951 UNITED STATES PATENT or-F ca TRIAGYL PHENYLPROPANEAM INODIOLS Harry M. Crooks, Jr., Mildred C. Rebstock, John Controulis, and Quentin R. 'Bartz, Detroit, Mich" assignors to Parke, Davis 8: Company,

Detroit, Mich, a corporation of Michigan No Drawing.

where R1 and R: are the same or diilerent and represent hydrogen, halogen, lower alkyl or lower alkoxy radicals and R3 is hydrogen or a lower alkyl radical. The term acyl as used herein includes saturated and unsaturated lower aliphatic acyl, halogen substituted lower aliphatic acyl, carboxy substituted lower aliphatic acyl, cyano substituted lower aliphatic acyl, ether substituted lower aliphatic acyl, hydroxy substituted lower aliphatic acyl, ester substituted lower aliphatic acyl, benzoyl, substituted benzoyl, araliphatic acyl, furoyl, pyridinoyl and the like radi- 09-18 It will be appreciated by those skilled in the art that the products and starting materials of the invention can exist in structural as well as optical isomeric forms. The term structural isomer or form as used herein refers to the cis or trans, that is, the planar relationship of the polar groups on the two asymmetric carbon atoms. To differentiate between these two possible diastereoisomers we will subsequently refer to the cis compounds as the regular [reg.] series or form' and to the trans diastereoisomers as the "pseudo [M series or form. Such cis compounds are products wherein the two most highly polar oi the groups on the asymmetric carbon atoms lie on the same side'of the plane of the two carbon atoms. Conversely, the trans or 'racemates of the optically active dextro [d] and 1W0 [ll rotatory isomers as as well as in the Application February SerialNo. 76,176

8 Claims. (Cl. 280-477) form of theindividual z or separated dextro [d] and levo [1] optical isomers. 1

Because of the difllculty of representing these structural diilerences in graphic formulae the customary structural formulae will be used in both the specification and claims and a notation placed; below or to the side of the formula to designate the particular structural and optical configuration of the compound. Where the formula represents the unresolved mixture of the structural and optical isomers the notation "unresolved will be used. However, it should be expressly understood that where no notation appears with a structural formula the formula should be interpreted in its generic sense, that is, as representing the [11-41, [dl-w, [ll-reg. or

where R1, R2 and R3 have the same significance as given above and R and R are the same or difl'erent and represent hydrogen or acyl radicals, R being hydrogen when R is hydrogen. As acylating agents acyl anhydrides or halides either alone or in conjunction with alkaline catalysts may be used. s

In carrying out the acylation under substantially anhydrous conditions with an acyl anhydride the reaction mixture is heated at about C. or above. When a temperature in the neighborhood of 100 C. is employed the heating is continued for at least one hour and preferably slightly longer. While at higher temperatures slightly less than one hour usually sufllces to bring about the reaction. When an alkaline substance or catalyst is employed the reaction can be carried out at about room temperature, that is, 20 to 35 C. although the mixture may be heated up to about 100 C., if desired. In most instances the reaction proceeds smoothly at about 20 to.

35' C.inthepresenceotanalkalinecatalystand hence the application of heat is not necessary and is preferably omitted.

when an acyl halide is used as the acylating agent in the presence of an alkaline substance either anhydrous or aqueous conditions may be employed In either case the reaction is carried out at'a temperature between about 15 and 50' C. but preferably in the range ofabout 20 to130 C. when aqueous conditions are used the alkaline catalyst should be chosen so that the acyl groups are not removed by hydrolysis during the reaction. Thus, in the case oi easily hydrolyaable acyl groups a weakly alkaline catalyst such as barium carbonate, sodium acetate, calcium carbonate, magnesium carbonate and the like should be used. However, when the acyl gro ps are a type more resistant to hydrolysis such as benzoyl or substituted benzoyl radicals, strongb alkaline catalysts such as sodium hydroxide and the like may be employed.

some specific examples oi the alkaline materials which can be used in the above described acylation p are-sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium car-' bonate, potassium carbonate, sodium bicarbonate, sodium acetate. pyridine, triethylamine, quinclin, N-ethyl morpholine, N-methyl piperidine, calcium hydroxide, calcium carbonate, barium carbonate, magnesium carbonate, barium hydroxide and the like.

The products of the invention are valuable intermediates for the preparation of other organic compounds. They are or particular value as intermediates in the preparation of organic compounds possessing antibiotic activity. For example, the products oi the invention which contain the pseudo structural form and no substituents in the phenyl ring can be converted by nitration.

hydrolysis, resolution [it necessary] and monodichloroacetylation to [ll--1-p-nitrophenyl-2-dichloroacetamidopropane-l,3-diol, a compound possessing outstanding and unique antibiotic activity.

The invention is illustrated by the following examples.

Example 1 1,3-di01 [M. P. 94 C.] having the formula,

on. 0 i=0 ran-(Leach [dll-Bcs. Iona [b] 2 g. of [d1] 11-1-phenyl-2-dichloroacetamidopropane-l,3-diol is added to a solution consisting of 5 cc. of pyridine and 5 cc. of acetic anhydride and the resulting mixture heated at 100 C. for one-halt hour. The reaction mixture is evaporated to dryness under reduced pressure, and the residue takenup in and crystallized iron 79' 0. Its formula is:

4 methanol. The product thus obtained is hill-ti;phenyl-2- dichloroacetamido-lJ-diacetoxypropane of formula,

Example 2 2 g. of [dlI-vIr-l-DhCDYl-Z-MtllfldO-3-M- oxypropane l-ol is added to a mixture composed oticaoiacetic l andaccoidrypyridine and the resulting mixture heated at 100' C. for one-halt hour. The reaction mixture is evaporated in vacuo and the residue recrystallized from methanol to obtain the trlacetate oi [dilvy-l-phenyl-z-aminopropane-lj-diol melting at A solution of 500 mg. of ill-ip-l-phenyl-zaminopropane-l,3-diol in 5 cc. of acetic anhydride is refluxed i'or three hours. The reaction mixture is evaporated to dryness in vacuo and the residue recrystallized from methanol. This compound has the formula,

CH: O

By substituting an equivalent amount 0! propionic anhydride for the acetic anhydride used in the above procedure, one obtain [ll-ip-l-phenyl-2-propionamido-1,3-dipropionyloxypropane.

Example 4 oLice water and the precipitate collected. The crude tribenzoate ot. [dll-ip-l-phenyl-ii-aminopropane-1,3-d1ol thus obtained;; -iswashed with sodium bicarbonate solution, water, dilute hydrochloric acid and finally with water. This prflduct which has the formula,

[dlJ-w Form may be purified by recrystallization from methanol.

of this product is:

a 5 v trample 5 10 g. of [d1] -reg.'-1'-phenyl-2-aminopropane- 1,3-diol is heatedwith' 'a mixture consisting of 20 cc. of pyridine and 20 cc. of acetic anhydride for .one-hali' hour at 100 0.:- The reaction mixture evaporated to drynessin' vacuo to-obtain the desired triacetateiMP. 115-8 0.] of [dl]'-reg;-

1-phe nyi-2-amincpropane-L8-diol of formula. on. o a 3 unit-on- 5 0- H O-Jm- .n-cmo -cm [dll-Beg. form Eeamplc 6 5 g. of either [d1] t-l-o-methylphenyl-2-acet- .amido-propane-1,3-diol or [dll-w-l-o-methylphenyl-z-acetamido ii-acetoxypropane 1 01 .is added to a mixture consisting of cc. of acetic anhydride and 10 cc. of pyridine and the resultinsmixture heated at 100 C. for about one-half hour. The reaction mixture is concentrated to dryness in vacuo' and the residual triacetate of ldll-w-l-o-methylphenyl-z-aminopropane 1.3 diol recrystallized-from methanol. The formula qinlnamim,

[rilli Form Example 7 6 g. of [d1] -reg.-1-o-methy1 phenyl-2-amino propane-1,3-diol is heated with 8 cc, of pyridine and 8 cc. of acetic anhydride for one hour at 100 C. and then the reaction mixture evaporated to dryness in vacuo. The residue thus obtained consome 6 trample 9 8 g. of [dl] reg.-1-[3',4'-dimethylphenyll-2 "aminopropane-Ls-diol' is heated at-100 C. for

one-half hour with a consisting of 16 cc. of acetic anhydride and 16 cc. of pyridine and the mixture evaporated to dryness in vacuo. The residue consists of the desired triacetate of [dilreg;-1- [3",4'-dimethyiphenyil-2 aminopro'pane- 1.8-dioi of formula.

a 7 (i=0 Nn- -cm pin-lineup 3-011 7 w rail-Reg. form' 0 is purified by recrystallization from ethanol.

I I Example 11 I 8 g. of [d1] ip-l-acetoxy-wacetamido-ii-phenylbutane-3-ol is heatedfor one hour at 100 C. with a mixture consisting 'of 16 cc. of acetic anhydride sists of the triacetate of [dl]-reg .-l-o-methylphenyl-2- aminopropane 1,3-diol of formula,

i=0 NH-ii-on,

Example 8 5 g. of [d1] t-f-m-methoxyphenyl-2-acetamido-Z-acetoxy-propane-l-ol is added to a mixture of 10 cc. of acetic anhydride and 10 cc. of pyridine. The resulting mixture is heated at 100 C. for one-half hour and then concentrated to dryness in vacuo. The residual triacetate of [dll--1-m-methoxypheny1 2 aminopropane- 1,3-diol is purified by recrystallization from ethanol. Its formulais:

CHI

[dill-w Form and 16 cc. of pyridine and then the reaction mixture evaporated to dryness in vacuo. The residue which consists of the triacetate of [dllqp-zamino-3-pheny1butane-1,3-dio1 is purified by recrystallization from ethanol. The formula for this product is:

CH: O J1=0 NH- pk-CHr i o c-jgglln-cnlo -om dl -11: Form I Example 12 10 g. of 1-o-chlorophenyl-2-aminopropane-1,3- diol is heated with a mixture composed of 30 cc. of pyridine and 30 cc. of acetic anhydride for about one-half hour at C. The reaction mixture is evaporated to dryness in vacuo and the residue washed with water. The water insoluble product thusobtained is the unresolved triacetate of 1-o-chlorophenyl-2-aminop1opane 1,3-diol. This compound which has the formula.

Unresolved Bastille 13 assaree 7 sl.oimethexyacetylchlorideisaddedsiowly- [till-Beg. form trample 14 g. of chilled chloroacetyl chloride is added slowly to a well stirred suspension consisting of 7 g. 01' calcium carbonate, 3.34 g. of [dll-t-lphenyl-2-aminopropane-i3-diol, 50 cc. oi! ethyl acetate and 60 cc. of water at 0' C. The reactionmixtureisstirredioroneandahali'hours, the ethyl acetate layer removed, dried and evaporated to dryness. The residue is crystallized from ethyl acetate-petroleum ether mixture to obtain virtually pure [dll-p-1-phenyl-2-chloroacetamido-l,3-di-(chloroacetoxy) propane o! formula,

& l o I H-CH Ol'l-GHgCl d1) at Form Example 8 g. of succinic anhydride is added to 4 g. of [d1]--l-phenyl-2-aminopropane-1,3-diol in 10 cc. 01' dry pyridine and the reaction mixture heated at 90-100 C. for one hour. 50 cc. 0t water is added. the pH of the solution adjusted to 2.5-3 with hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract is washed with dilute hydrochloric acid and with 0.1 volume of water. The ethyl acetate extract is dried, the ethyl acetate distilled and the realdue consisting of the desired 1,2.3-trisuccinoyl derivative of [d1]--1-phenyl-2-aminopropanel,3-diol purified by crystallization from water.

The formula of this product is:

CODE

[ l-W Form I his, re

4cc.oiacetic anhydrideisaddedtoasolution consisting o! 2 g. or [ll-w-l-phenyl-i-qyameetamidopropane-lfi-diol in 10 cc. of dry pyridine. The reaction mixture is allowed tostand for four hours at room temperaturaltreated withlea. ct

warm waterandevaporamdtodrynelinvacuo. Crystallization vo! the residue from ether-petroleum ether mixture yields the desired [ll-i- 1-phenyl-2-cyanacetamido-13-diacetowpropana oi the formula,

CE: I O =0 NH-a-clhcN Gin-la-chmi-cm I ill-i I'orm Icample 17 6cc.oiacetic nhydrideisaddedto2.5s.oi lll-w-l-phenyl-2 -lactamidopropane-1,3-diol in 10 cc. of dry pyridine-and the mixture heated at 90-100 C. for one-hall hour. Sec. of water h added. the reaction mixture evaporated to dryness and the residue crystallized from etherpetroleum ether mixture to obtain the desired [1] P'l phenyl 2 acetoxylactamido IA-diacetoxypropane of formula,

[ll-W Example 18 3.5 z. of benzoyl chloride is added in small portions to a vigorously shaken suspension of 2' g. 01' [d1] --l-phenyl-2=p,p-dimethylacrylamidopropane-1.3-diol in 40 cc. of cold 1 N sodium hydroxide solution. During the addition the temperature is maintained below 30 C. After the odor of benzoyl chloride has disappeared the solid product is collected and recrystallized from aqueous methanol to obtain the desired [dll-W-lphenyl-2-,s,p-dimethylacrylamido-1,3 dibensoyloxypropane-oi formula,

[dll-xl: Form Example 19 A solution 01' 1.1 g. of ill-ip-l-phenyl-2- aminopropane-1,3-diol in 50 cc. of ethyl acetate is shaken with 5 g. of p-nitrobenzoyl chloride and sufllcient 1 N sodium hydroxide solution to maintain the pH at 8-10. When further additions of alkali show the acid chloride to be completely reacted, the ethyl acetate layer is separated. washed with water, dried and evaporated. The

solid residue consists 0! the desired 1.3,3-1-9- nitrobenzoyl derivative of [ll--1-phenyl-2- aminopropane-L3-diol oi i'ormula,

[11-41 Form By substituting 3,4-dlchlorobenzoyl chloride for the p-nitrobenzoyl chloride used in the above example, one obtains the corresponding 1,2,3- tri-3,4-dichlorobenzoyl derivative 01' [l]-\//-1- phenyl-2-aminopropane-1,3-diol. I! desired, an equivalent amount 01' p-methylbenzoyl chloride can be substituted for the p-nitrobenzoyl chloride to obtain the 1,2,8-tri-p-methylbenzoyl derivative of [l] 0-1-pheny1-2-aminopropane-1,3-diol.

Example 20 v f. NH E CH@ I gaalmmianlo [dll-xl/ Form is purified by crystallization from methanol.

Example 21 A mixture consisting of 1.67 g. 01 [d1] -reg.-1- phenyI-Z-aminopropane-1,3-d101, 8 g. of i'uroic anhydride, and 15 cc. of dry pyridine is heated for one-half hour at 90400 C. cc. of water is added and then the reaction mixture diluted with 100 cc. of ethyl acetate. The ethyl acetate solution is washed successively with dilute hydrochloric acid, sodium bicarbonate solution and water. The ethyl acetate layer is dried and the ethyl acetate distilled to obtain the desired [d1]- reg. 1 phenyl 2 furoamido 1,3 diiuroyloxypropane of formula,

*1. U E LCMEU [an-Reg. form' This product may be purified by recrystallization from methanol.

10 Example 22 1.67 g. of ldil-w-1-phenyl-z-aminopropane- 1.3-diol in 30 cc. of ethyl acetate is added slowly to 7 g. of nicotinoyl chloride hydrochloride in 30 cc. of dry ethyl acetate. 5 g. of pyridine is added slowly to the mixture, keeping the temperature in the neighborhood of about 10 C. After stirring for one hour, 5 cc. of water is added. the ethyl acetate layer separated and washed with water. The ethyl acetate extract is dried, concentrated to a volume 01' about 10 cc. and diluted with ligroin. After some time the desired 1,2,3- tri-nicotinoyl derivative of [dll-c-i-phenyl-2- aminopropane-l.3-diol separates from the solution in crystalline form. This product has the formula,

Q NH-LO 3 0 -JIH H-(JmO-PJU [tn-1P Form Example 23 A solution consisting of 1.8 g. of [d1]reg.-1- phenyl-2-bromacetamidopropane- 1,3-dial in 10 cc. of acetic anhydride is heated under reflux for about twenty minutes. The excess acetic anhydride and acetic acid are removed by distillation in vacuo and the residue crystallized from ether-petroleum ether mixture to obtain the desired [dl]-reg.-1-phenyl-2-bromacetamido-1,3- diacetoxypropane. This product has the formula,

i.. lH CH.OE CH.

[till-Reg. form Example 24 9 g. of phthalic anhydride'is added to a solution of 3 g. of [d1]-1//-1-phenyl-2-aminopropane- 1,3-dial in 10 cc. of dry pyridine and the mixture heated at about C. for one hour. 50 cc. of water is added, the pH of the solution adjusted to about 3 with hydrochloric acid and the mixture extracted with ethyl acetate. The ethyl acetate extract is washed with dilute hydrochloric acid. with a small amount of water, and then dried. The ethyl acetate is removed by distillation in vacuo to obtain the desired 1,2,3-triphthaloyl derivative of [d1] b 1 phenyl-2- aminopropane-L3-diol of the formula,

In the foregoing examples we have employed a new class of amino diols and their mono and ll diacyl derivatives as starting materials. These starting materials can be prepared in a number of different ways. One of the general methods which can be used to'prepare these products is 1 ggo-i imi-cmorr 3 H NH-Aeyl grammes...

F ln.

where R1, R: and Re have the same significance as given above.

, Where optically active starting .materials are desired the racemic structural forms of the free amino diols are resolved into their optical isomers via an optically active acid addition salt, suitable acids being [dl-tartaric, EdJ-camphor sulfonic, [d] -bromocamphor suli'onic and [d] -mandelic. The optically active amino diols so obtained can be used as starting materials per se or converted by acylation, as shown above, to the optically active monoand di-acyl starting materials of the invention. Where an unresolved starting material is desired the separation into the structural forms shown on the diagram is omitted. The following examples serve to illustrate the application of this general method to the preparation of some of the specific starting materials used in the foregoing examples.

Example 25 1.1 g. of sodium is dissolved in 20 cc. of methanol and the resulting solution added to a solution of 5 g. of benzaldehyde and 4.5 g. of p-nitroethanol in cc. of methanol. After standing at room temperature for a short time t e 1 on NH-Acyl Q-iT-Jm-cmOB propane-1,3-diol. If desired, the free nitro diol having the formula.

OH NO:

Unresolved can be obtained byacidiflcation of the salt.

20 g. of the sodium salt of l-phenyl-2-nitropropane-1.3-dio1 [prepared by the above method] is dissolved in 200 cc. of glacial acetic acid. 0.75 g. of palladium oxide hydrogenation catalyst is added and the mixture shaken with hydrogen under three atmospheres pressure for about twelve hours. The catalyst is removed by filtration, the'flltrate concentrated to about one-tenth volume in vacuo and diluted with five volumes of water. The solution is extracted with one volume of ethyl acetate or ether and the extract discarded. The aqueous phase is made alkaline to pH 12 with strong sodium hydroxide solution and extracted with five cc. portions of ethyl acetate. The combined extracts are dried. the ethyl acetate evaporated and the residue recrystallized from chloroform. The white crys- 16 talline product thus obtained is [dll -reg.-l-phenyl-z-aminopropane-lfi-diol [11. 2. 103-4 6.] of formula,

(GD-B01. form The chloroform filtrate from the crystallization of the [d1]-reg.-1-phenyl-2-aminopropane- 1,3-diol is evaporated to dryness and the residue heated with an excess of acetic anhydride at 70 C. for fifteen minutes. The reaction mixture is evaporated to dryness in vacuo and the residue recrystallized from ethanol. This white crystalline product which melts at 167-8 C. is [d1] -l-phenyl-2-acetamido-3-acetoxypropanel-ol. It can be represented by the following formula,

o mp -cm on i o 'JH- Emmot -0H; [d1]-l1 Form If desired, the [dll -1l/-1-phenyl-2-aminopropane-1,3-diol can be separated from the starting material used in the above procedure by fractional crystallization. This same product can also be obtained by hydrolysis of the pure [d1]-4P1- phenyl-2-acetamido-3-acetoxypropane prepared above. This latter procedure is illustrated in the next example.

Example 26 4 g. of [d1]-\l/-1-phenyl-2-acetamido-3-acetoxypropane-l-ol in 25 cc. of 3 N hydrochloric acid is refluxed for about three hours and the reaction mixture evaporated to dryness .in vacuo. The residual hydrochloride salt is taken up in a small amount of water, the solution made alkaline with sodium hydroxide and extracted with ethyl acetate. After drying, the ethyl acetate is evaporated from the extracts in vacuo to obtain the free base of [d1]--1-phenyl-2-aminopropane-1,3-diol; M. P. 86-7 C. This product has the formula,

OH NH2 (an-w Form The free base of [d1]--l-phenyl 2-aminopropane-1,3-diol obtained above is dissolved in 60 cc. of warm n-butanol containing 5' g. of [dl-camphor sulfonic acid and the mixture cooled. The solid which separates is collected, recrystallized twice from n-butanol and dissolved in a small amount of water containing an excess of sodium hydroxide. The solution is extracted with ethyl acetate, the ethyl acetate extracts dried and the solvent distilled in vacuo. The residue which consists of [ll--1-phenyl-2-aminopropane-1,3-diol has the formula,

2 g. of [l]--1-phenyl-2-aminopropane-1,3- diol is heated with an excess of acetic anhydride at 75 C. for about fifteen minutes. The reaction mixture is evaporated to dryness in vacuo at low temperature and the residue crystallized from 14 ethanol to obtain the desired tll'lllfl'fllml'z' acetamido-ii-acetoxypropane-l-ol of formula,

0 NH-a-CH;

on i o O-tn- H-CHlOH-OHO [ll-1P Form .residue from ethylene dichloride, yields the desired [l]-p-1-phenyl-Z-acetamidopropane-1,3- diol of formula,

[11-11 Form Example 27 2 g. of [d1] -reg.-l-phenyl-z-acetamidopropane- 1,3-diol is heated with an excess of acetic anhydride at 70 C. for a short time. The reaction mixture is evaporated to dryness in vacuo and the residual [d1]-reg.-1-phenyl-2-acetamido-3- acetoxypropane-l-ol purified by recrystallization from ethanol. This product's formula is:

(an-Reg. form 1.7 g. of [dl]-reg.-l-phenyl-2-aminopropane- 1,3-diol is treated with 1.6 g. of methyl dichioroacetate and the mixture heated at C. for one and one-quarter hours. The residue is washed with two 20 cc. portions of petroleum ether and theinsoluble product collected. Recrystallization from ethyl acetate yields the desired [dll-reg.-1-

phenyl-2-dichloroacetamidopropane-1,3-diol in pure form; M. P. 1589 C. This product's formula is: I V

I I OCH-CH-CHzOH (an-ne form Example 28 3'rl-2-- nitropropane-1,3 -cliol; which has the formula,

on 'NO:

QcH-en-cmon Unresolved 18 g. of the sodium salt of l-o-methylphenyl- 2-nitropropane-l,3-diol is dissolved in 175 cc. of glacial acetic acid, 0.75 g. of palladium oxide hydrogenation catalyst added and the mixture hydrogenated under three atmospheres pressure of hydrogen for about twelve hours. The catalyst is removed by filtration, the filtrate concentrated to a small volume in vacuo and then the residue diluted with five volumes of water. The solution is extracted with one volume of ethyl acetate or ether and the extract discarded. The aqueous phase is made alkaline to pH 12 with strong sodium hydroxide solution and extracted with five volumes of ethyl acetate. The ethyl acetate extracts are combined, dried and the ethyl acetate evaporated in vacuo. The residue which consists of a mixture of the [till-reg. and [dl] l/ 1 o methylphenyl 2 aminopropane-1,3-diol is taken up in and crystallized from chloroform to obtain the [d1]-reg.-1-omethylphenyl-2-aminopropane-1,3-diol in crystalline form. Its formula is:

H NH:

Quite...

[dlJ-Beg. form The chloroform filtrate from which the [d1]- reg. 1 o methvlphenyl 2 aminopropane- 1,3-diol has been removed is evaporated in vacuo to obtain the crude EdH-yb-I-O-methyIphenyI- 2-aminopropane-1,3-diol.

The crude [d1]--1-o-methylphenyl-2-aminopropane-1,3-diol is treated with an excess of acetyl chloride at about room temperature in a QJlH-JEH-CILOH [dlHP Form 3 g. of crude idll-w-l-o-methylphenyl-2- aminopropane-1,3-diol is heated with an excess of acetic anhydride at about 70 to 80 C. for fifteen minutes and then the reaction mixture evaporated in vacuo. The residue which con- 16 sists of [d1] b-l-oemethylphenyl-2-acetamido- 3-acetoxypropane-l-ol has the formula,

QZZJMMLK.

, [an-w Form and is purified by recrystallization from-ethanol.

Example 29 The starting materials having as the root of their formulae the structure,

A) NH- can be obtained by starting with m-methoxybenzaldehyde and p-nitroethanol and applying the procedures described in Examples 25, 26 and 27.

Example 30 The starting materials which have as the root of their formulae the structure,

The compounds used as starting materials in the preparation of the amino diols having the general formula,

332cm... Ch

are prepared by starting with acetophenoneand p-nitroethanol and following the procedures described in Examples 25, 26 and 27.

Example 32 The products used as starting materials havin as the root of their formulae the structure,

can be prepared from o-chlorobenzaldehyde and p-nit'roethanol using the procedures described in Examples 25, 26 and 27. However, the reduction 01' the 1-o-chlorophenyi-2-nitropropane-1,3-diol intermediate is preferably carried out by the use of stannous acetate or chloride in acetic acid rather than by the use of the catalytic means shown in the aforementioned examples.

Some of the subject matter disclosed but not claimed herein. is disclosed and claimed in our copending applications filed on even date herewith, Serial Nos. 76,172, 76,173, 76,174, 76,175, 76,177 (now Patent No. 2,514,376), 76,178 (now Patent No. 2,514,377), 76,179 (new Patent No. ,483,885) and 76.180.

' What we claim is: 6; A compound or the formula,

1. A compound or the formula, 4 0

' 2 E (Lo mr-a-onch BUILT-- HCHr0Aoyl 8 J o Oon n-cmo -om where R1 and R: are members of the class con- 'sisting of hydrogen, halogen, lower alkyl and ran-w Form lower lko rdl lsadRais mber o1 the class gg g gi 1121mm 2: m1 '1. 1-phenyl-2-(dichloroacetamido)-1,8-diacetoxy-propane. $3215, said acyl being a carboxylic acid say! 8. A compound of the formula 2. A compound of the formula,

OAcyl NH-Acyl said acyl being a carboxylic acid acyl radical. v o= 3. A compound of the formula, l

MMJF

. J) 0 1 HARRY M. cnooxs, 4n.

OJminnin -cm 311101151 0. mm. r om: mm v1.15. 4. A compound or the formula, 25 QUENTIN R. 3mm.

i CH Banal-mores cl'rlzn The toilo'wing references are of record in the l 30 file of this patent: Q UNITED s'm'ms mm mm Number Name nm 5. A compound of the formula. 2,108,266 Lott Dec. 28, 1937 CH; 0 35 (5:0 NHS-CHI v Oin-Jm-cmoE-om o ran-an. m 

1. A COMPOUND OF THE FORMULA,
 8. A COMPOUND OF THE FORMULA, 